Abstract
Purpose: Aim of this study was to develop a multi-gene signature to help better predict prognosis for stage III renal cell carcinoma (RCC) patients.Methods: Fourteen pairs of stage III tumor and normal tissues mRNA expression data from GSE53757 and 16 pairs mRNA expression data from TCGA clear cell RCC database were used to analyze differentially expressed genes between tumor and normal tissues. Common different expressed genes in both datasets were used for further modeling. Lasso Cox regression analysis was performed to select and build prognostic multi-gene signature in TCGA stage III kidney cancer patients (N = 122). Then, the multi-gene signature was validated in stage III renal cancer cases in Fudan University Shanghai Cancer Center (N = 77). C-index and time-dependent ROC were used to test the efficiency of this signature in predicting overall survival.Results: In total, 1,370 common different expressed genes were found between tumor and normal tissues in both datasets. After Lasso Cox modeling, nine mRNAs were finally identified to build a classifier. Using this classifier, we could classify stage III clear cell RCC patients into high-risk group and low-risk group. Prognosis was significantly different between these groups in discovery TCGA cohort, validation FUSCC cohort and entire set (All P < 0.001). Multivariate cox regression in entire set (N = 199) revealed that risk group classified by 9-gene signature, age of diagnosis, pN stage and ISUP grade were independent prognostic factor of overall survival in stage III kidney cancer patients.Conclusion: We developed a robust multi-gene classifier that can effectively classify stage III RCC patients into groups with low and high risk of poor prognosis. This signature may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy.
Highlights
Kidney cancer is one of the most common urological tumors worldwide, and nearly 65,340 new cases and 14,970 deaths were estimated in the United States in 2018 [1]
We focused on prognosis prediction for stage III Clear cell renal cell carcinoma (ccRCC) patients and constructed a nine-gene signature, using data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases
We found that risk group was an independent prognostic factor at the discovery stage (HR: 10.460; 95% confidence interval (CI): 4.252–25.734; P < 0.001), validation stage (HR: 10.204; 95% CI: 3.969–26.234; P < 0.001), and entire set (HR: 9.874; 95% CI: 5.234–18.629; P < 0.001)
Summary
Kidney cancer is one of the most common urological tumors worldwide, and nearly 65,340 new cases and 14,970 deaths were estimated in the United States in 2018 [1]. Prognostic prediction is mainly based on pathological stages of RCC patients [3]. The tumor node metastasis (TNM) classification system is recommended for tumor staging in clinical practice [4]. Obvious survival differences exist between the subgroups of stage III RCC patients (T3N0M0, 5-year survival: 20–70%; T1-3N1M0, 5-year survival: 0–20%) [5]. The latest edition (8th) of the UICC/AJCC TNM staging system has been released, this problem remains unsolved, and limits the application of this system in estimating prognosis to direct clinical practice. Better signatures are required to help predict prognosis for stage III RCC patients
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